NSF-BSF: Synchronous electro-optical DNA detection using low-noise dielectric nanopores on sapphire

NSF-BSF：使用蓝宝石上的低噪声介电纳米孔进行同步电光 DNA 检测

• 批准号: 2020464
• 负责人: Chao Wang
• 金额: $ 36万
• 依托单位: Arizona State University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2020464&HistoricalAwards=false
• 关键词: NSF; BSF; Synchronous; electro; optical

Nanopore DNA sensing is an emerging technology, and has recently been developed to detect both the DNA primary sequence and epi-genetic information (such as methylation), which is crucial to both fundamental biology and precision medicine.. However, high-speed and accurate DNA methylation detection in nanopores still lags behind. This is attributed to an insufficient signal-to-noise ratio (SNR) resulting from the inherent large electrical capacitive noise from the conductive silicon (Si) and also the complex DNA dynamic interaction with nanopore surface. This project proposes a multidisciplinary research plan to address the fundamental challenges in high-speed and low-noise biomolecular sensing in a solid-state nanopore device. The new design combines electrical and optical sensing on a single sensor platform to improve the sensing accuracy. It utilizes crystalline sapphire as an insulating substrate and integrates large-bandgap titanium oxide thin film as the sensing element to minimize both the electronic and optical noise. The demonstration of DNA methylation detection will prove the feasibility of our TiO2/sapphire nanopore sensors in detecting complex molecular structures that will have broad impact on molecular marker detection and molecule-molecule interactions. The educational objectives are to promote electronic nanosensors related engineering education to undergraduate and graduate students, and to better prepare them as future innovators to transform nanobiotechnologies. The outreach objectives are to promote public awareness of the importance of nanosensors in health care and to attract the participation of K-12 students and underrepresented individuals in STEM careers.This research is to fill the knowledge gap in nanopore sensing research by creating a significantly improved nanopore sensor platform that integrates low-optical background titanium oxide membranes on low-capacitance and hence low-electrical-noise sapphire. The research team will fabricate small and thin TiO2 membranes on sapphire, establish high-throughput manufacturing methods for both membrane formation and nanopore drilling, perform single-molecule DNA translocation, study the DNA-nanopore interaction, and analyze the data for methylation detection. The proposed sensor platform has a number of key features to support the development of a wide variety of emerging biomolecular diagnostic technologies. First, the creation of ultrasmall (10 μm) dielectric membranes on insulating sapphire eliminates substrate conductance, and drastically minimizes the chip capacitance to a few picoFarads even for high-dielectric-constant and ultrathin (5 nm) TiO2 devices, thus significantly reducing the background high-frequency electrical noise and markedly improving high-bandwidth sensing. Further, both membrane formation and nanopore drilling will be achieved by high-throughput manufacturing methods, i.e. wafer-scale and batch-processing compatible sapphire etching and direct laser drilling, thus enabling low-cost and repeatable production. The scalably manufactured, low-noise, high-sensitivity nanopores will facilitate high-resolution gene identification and quantitation of their methylation status in a single measurement and at a greatly reduced cost.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

纳米孔DNA传感是一项新兴技术，最近被开发用于检测DNA初级序列和表观遗传信息（如甲基化），这对于基础生物学和精准医学都至关重要。然而，纳米孔中高速、准确的DNA甲基化检测仍然滞后。这是由于导电硅 (Si) 固有的大电容噪声以及 DNA 与纳米孔表面复杂的动态相互作用导致信噪比 (SNR) 不足。 该项目提出了一项多学科研究计划，以解决固态纳米孔器件中高速和低噪声生物分子传感的基本挑战。新设计将电气和光学传感结合在单个传感器平台上，以提高传感精度。它利用晶体蓝宝石作为绝缘基板，并集成大带隙氧化钛薄膜作为传感元件，以最大限度地减少电子和光学噪声。 DNA甲基化检测的演示将证明我们的TiO2/蓝宝石纳米孔传感器在检测复杂分子结构方面的可行性，这将对分子标记检测和分子-分子相互作用产生广泛影响。教育目标是向本科生和研究生推广电子纳米传感器相关的工程教育，并让他们更好地成为未来纳米生物技术变革的创新者。推广目标是提高公众对纳米传感器在医疗保健中重要性的认识，并吸引 K-12 学生和代表性不足的个人参与 STEM 职业。这项研究旨在通过创建一个显着改进的纳米孔传感器平台来填补纳米孔传感研究的知识空白，该平台将低光学背景氧化钛膜集成在低电容上，从而实现低电噪声 蓝宝石。研究团队将在蓝宝石上制备小而薄的TiO2膜，建立成膜和纳米孔钻取的高通量制造方法，进行单分子DNA转位，研究DNA-纳米孔相互作用，并分析甲基化检测的数据。所提出的传感器平台具有许多关键功能，可以支持各种新兴生物分子诊断技术的开发。首先，在绝缘蓝宝石上创建超小型（10μm）介电膜消除了衬底电导，即使对于高介电常数和超薄（5nm）TiO2器件，也能将芯片电容大幅降至几皮法，从而显着降低背景高频电噪声并显着改善高带宽传感。此外，成膜和纳米孔钻孔都将通过高通量制造方法来实现，即晶圆级和批量处理兼容的蓝宝石蚀刻和直接激光钻孔，从而实现低成本和可重复生产。可大规模制造、低噪音、高灵敏度的纳米孔将有助于在单次测量中以极大降低的成本进行高分辨率基因识别和甲基化状态定量。该奖项反映了 NSF 的法定使命，并通过使用基金会的智力优点和更广泛的影响审查标准进行评估，被认为值得支持。

项目成果

Picomolar-Level Sensing of Cannabidiol by Metal Nanoparticles Functionalized with Chemically Induced Dimerization Binders

通过化学诱导二聚化粘合剂功能化的金属纳米颗粒对大麻二酚进行皮摩尔水平传感

• DOI: 10.1021/acssensors.3c01758
• 发表时间: 2023
• 期刊: ACS Sensors
• 影响因子: 8.9
• 作者: Ikbal, M. D.;Kang, Shoukai;Chen, Xiahui;Gu, Liangcai;Wang, Chao
• 通讯作者: Wang, Chao

Sapphire-supported nanopores for low-noise DNA sensing

用于低噪声 DNA 传感的蓝宝石支撑纳米孔

• DOI: 10.1016/j.bios.2020.112829
• 发表时间: 2021
• 期刊: Biosensors and Bioelectronics
• 影响因子: 12.6
• 作者: Xia, Pengkun;Zuo, Jiawei;Paudel, Pravin;Choi, Shinhyuk;Chen, Xiahui;Rahman Laskar, Md Ashiqur;Bai, Jing;Song, Weisi;Im, JongOne;Wang, Chao
• 通讯作者: Wang, Chao